Heterocyclic compounds for the treatment of disease

Abstract

Described herein are heterocyclic compounds, compositions, and methods for their use for the treatment of disease.

What is claimed is: 
     
       1. A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         X 1 , X 2 , X 3 , and X 4  are each CR 1 ; 
       
       
         
           
           
               
               
           
         
       
       is selected from 
       
         
           
           
               
               
           
         
         Z is —O—, —S—, —N(R 4 )—, —CH 2 —, —OCH 2 —, or —CH 2 O—; 
         each R 1  is independently selected from the group consisting of hydrogen, halogen, and CF 3 ; 
         each R 2  is independently selected from the group consisting of halogen and optionally substituted C 1 -C 6 alkyl; 
         R 3  is selected from the group consisting of hydrogen and optionally substituted C 1 -C 6 alkyl; 
         R 4  is hydrogen or optionally substituted C 1 -C 6 alkyl; 
         n is 0-4; and 
         p is 1. 
       
     
     
       2. The compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein 
       
         
           
           
               
               
           
         
       
     
     
       3. The compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein 
       
         
           
           
               
               
           
         
       
     
     
       4. The compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein Z is —O—, —OCH 2 —, or —CH 2 O—. 
     
     
       5. The compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein Z is —O—. 
     
     
       6. The compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein Z is —OCH 2 —. 
     
     
       7. The compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2. 
     
     
       8. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient or binder, and a compound of  claim 1 ; or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       9. A method of agonizing sphingosine-1-phosphate (S1P) receptor activity comprising contacting the S1P receptor, or portion thereof, with a compound, or a pharmaceutically acceptable salt or solvate thereof, according to  claim 1 . 
     
     
       10. A method of treating ulcerative colitis or Crohn's disease in a mammal that would benefit from sphingosine-1-phosphate (S1P) receptor agonism comprising administering to the mammal a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or solvate thereof, according to  claim 1 . 
     
     
       11. The compound of  claim 1  that is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       12. The compound of  claim 1  that is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       13. The compound of  claim 1  that is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       14. The compound of  claim 1  that is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof.